Abstract: This second part of a two-part series focuses on a discussion of progesterone and progestins differentiating the two in terms of synergy between estradiol and progesterone, balance between estrone and estrogen sulfate within tumor cells, protection of the uterine linings and impact on cardiovascular function; and bioidentical progesterones (oral and topical). Sidebars provide examples of studies showing adverse effects of medroxyprogesterone acetate on cardiovascular health, progesterone’s beneficial effects on cardiovascular function, results with bioidentical progesterone, results with topical progesterone and a protocol for combined hormone replacement therapy using progesterone skin cream. The authors conclude that physicians should not turn their backs on patients suffering from hormonal deficiencies in the absence of large clinical trials with bioidentical hormones since the literature suggests estradiol and estriol would be good estrogens to use and transdermal delivery of hormones is advantageous over oral delivery. With oral delivery, doctors should rethink dosing and consider impact on other relevant parameters. It appears that certain progestins should be avoided in favor of bioidentical progesterone, and saliva testing can allow monitoring of hormone levels. With good follow-up, clinical judgment and laboratory backup, there is enough information about hormone replacement to offer bioidentical hormone replacement therapy as a viable option. A patient handout on hormone replacement therapy accompanies the article.